Mutation spectra induced by adozelesin in the supF gene of human XP-A fibroblasts

Adozelesin is a synthetic analog of the antitumor antibiotic, CC-1065, which alkylates N3 of adenine in the minor DNA groove in a sequence-specific manner. Here we tested the mutation spectra induced by adozelesin in the supF gene of human XP-A fibroblasts using a shuttle vector assay. Adozelesin pr...

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Bibliographic Details
Published in:Archives of pharmacal research 2010, 33(4), , pp.633-636
Main Authors: Lee, Se-Young, Pfeifer, Gerd P., Lee, Chong-Soon
Format: Article
Language:English
Subjects:
Antineoplastic Agents, Alkylating - pharmacology
Cell Line, Transformed
Cyclohexanecarboxylic Acids - pharmacology
Cyclohexenes - pharmacology
Fibroblasts - drug effects
Fibroblasts - metabolism
Genes, Suppressor
Humans
Indoles - pharmacology
Medicine
Mutation
Pharmacology/Toxicology
Pharmacy
Plasmids
RNA, Transfer - genetics
약학
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Summary:Adozelesin is a synthetic analog of the antitumor antibiotic, CC-1065, which alkylates N3 of adenine in the minor DNA groove in a sequence-specific manner. Here we tested the mutation spectra induced by adozelesin in the supF gene of human XP-A fibroblasts using a shuttle vector assay. Adozelesin primarily induces mutations via an A → T transversion and a single base insertion. The A → T transversion (43/59) was observed at the adenine alkylation site in the 5′-ATTTA* sequence (A* is the site of alkylation). The single base insertion (5/59) was observed at the 3′-side of the covalently modified adenine in the 5′-CTAAA* sequence. The results of this study suggest that the DNA alkylating sequence of adozelesin influences the type of DNA mutation.
ISSN:0253-6269
1976-3786
DOI:10.1007/s12272-010-0419-7